Background
DHPG ((RS)-3,5-DHPG) is an amino acid that is a selective potent agonist for group I mGluR (mGluR 1 and mGluR 5) and has no effect on Group II and III mGluR [1，6]. DHPG ((RS)-3,5-DHPG) is also a potent antagonist of mGluRs associated with phospholipase D[2].
(RS)-3,5-DHPG (10μM) treatment induced Müller cell gliosis, as evidenced by enhanced GFAP expression. In addition, (RS)-3,5-DHPG (10 and 100μM) treatment induced a transient decrease in Kir4.1 mRNA expression in the cells. Activation of mGluR I by (RS)-3,5-DHPG may decrease the number of functional Kir4.1 channels in purified cultured rat retinal Müller cells through modulating Kir4.1 protein and mRNA, thus contributing to Müller cell gliosis[5].
Impairments of spatial memory induced by bilateral infusions of (RS)-3,5-DHPG (50 μmol) into the CA1 area. Dose-dependent changes in spatial memory induced by (RS)-3,5-DHPG infusion. Pre-infusion of MPEP or CID755673 prevented impairments of spatial memory induced by (RS)-3,5-DHPG infusion[3]. Hippocampal GPR30 expression was reduced in middle-aged mice compared with young adult mice. a group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-DHPG -induced long-term depression in mossy fiber-cornu ammonis 3 (MF-CA3) synapses but not SC-CA1 synapses was facilitated in brain slices from G1-treated middle-aged mice[4]. (RS)-3,5-DHPG elicited acute mechanical allodynia and thermal hyperalgesia in na?ve mice from 1 h to 12 h following intrathecal (central/spinal) administration.The attenuation of intrathecal (RS)-3,5-DHPG -evoked acute pain by artesunate therapy in rats[7].
参考文献:
[1]: Winder DG, Conn PJ. Metabotropic glutamate receptor (mGluR)-mediated potentiation of cyclic AMP responses does not require phosphoinositide hydrolysis: mediation by a group II-like mGluR. J Neurochem. 1995 Feb;64(2):592-9. doi: 10.1046/j.1471-4159.1995.64020592.x. PMID: 7830052.
[2]: Pellegrini-Giampietro DE, Torregrossa SA, Moroni F. Pharmacological characterization of metabotropic glutamate receptors coupled to phospholipase D in the rat hippocampus. Br J Pharmacol. 1996 Jun;118(4):1035-43. doi: 10.1111/j.1476-5381.1996.tb15503.x. PMID: 8799579; PMCID: PMC1909512.
[3]: Wang W, Duclot F, et,al. Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats. PLoS One. 2018 Apr 3;13(4):e0195095. doi: 10.1371/journal.pone.0195095. PMID: 29614089; PMCID: PMC5882104.
[4]: Xu W, Cao J, et,al. GPR30 activation improves memory and facilitates DHPG-induced LTD in the hippocampal CA3 of middle-aged mice. Neurobiol Learn Mem. 2018 Mar;149:10-19. doi: 10.1016/j.nlm.2018.02.005. Epub 2018 Feb 6. PMID: 29421611.
[5]: Gao F, Li F, et,al. Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal Müller cells. Neurosci Lett. 2015 Feb 19;588:12-7. doi: 10.1016/j.neulet.2014.12.048. Epub 2014 Dec 27. PMID: 25549543.
[6]: Ito I, Kohda A, et,al. 3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate receptors. Neuroreport. 1992 Nov;3(11):1013-6. PMID: 1362358.
[7]: Zhang L, Zhao Y, et,al.Artesunate Reduces Remifentanil-induced Hyperalgesia and Peroxiredoxin-3 Hyperacetylation via Modulating Spinal Metabotropic Glutamate Receptor 5 in Rats. Neuroscience. 2022 Apr 1;487:88-98. doi: 10.1016/j.neuroscience.2022.01.003. Epub 2022 Jan 11. PMID: 35026318.
DHPG ((RS)-3,5-DHPG) 是一种氨基酸，是 I 组 mGluR（mGluR 1 和 mGluR 5）的选择性强效激动剂，对 II 组和 III 组 mGluR 没有影响 [ 1，6]。 DHPG ((RS)-3,5-DHPG) 也是与磷脂酶 D[2] 相关的 mGluRs 的有效拮抗剂。
(RS)-3,5-DHPG (10μM) 处理可诱导 Müller 细胞神经胶质增生，增强的 GFAP 表达证明了这一点。此外，(RS)-3,5-DHPG（10 和 100μM）处理诱导细胞中 Kir4.1 mRNA 表达的瞬时降低。 (RS)-3,5-DHPG 激活 mGluR I 可能通过调节 Kir4.1 蛋白和 mRNA 减少纯化培养的大鼠视网膜 Müller 细胞中功能性 Kir4.1 通道的数量，从而促进 Müller 细胞神经胶质增生[ 5].
向 CA1 区域双侧输注 (RS)-3,5-DHPG (50 μmol) 会导致空间记忆受损。 (RS)-3,5-DHPG 输注引起的空间记忆的剂量依赖性变化。预输注 MPEP 或 CID755673 可防止 (RS)-3,5-DHPG 输注引起的空间记忆损伤[3]。与年轻的成年小鼠相比，中年小鼠的海马 GPR30 表达降低。 I 组代谢型谷氨酸受体 (mGluR) 激动剂 (RS)-3,5-DHPG 在苔藓纤维-角氨 3 (MF-CA3) 突触中诱导长期抑制，但在脑切片中促进了 SC-CA1 突触G1处理的中年小鼠[4]。 (RS)-3,5-DHPG 在鞘内（中央/脊髓）给药后 1 小时至 12 小时内在幼稚小鼠中引起急性机械异常性疼痛和热痛觉过敏。鞘内（RS）-3,5-DHPG 诱发的急性青蒿琥酯治疗大鼠的疼痛[7].
Protocol
| Cell experiment [1]: |
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Cell lines
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Müller cell
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Preparation Method
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(RS)-3,5-DHPG treatment induced the purification of cultured rat retinal Muller cells.
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Reaction Conditions
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(RS)-3,5-DHPG (10 μM) for 0.5-24 h.
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Applications
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(RS)-3,5-DHPG treatment induced down-regulation of Kir4.1 protein in cell membrane compartments of Muller cells.
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| Animal experiment [2]: |
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Animal models
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Adult male Sprague Dawley rats (250-280 g)
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Preparation Method
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To determine mechanisms underlying the effects of (RS)-3,5-DHPG infusion, some animals received two consecutive infusions conducted 10 min apart. Rats in these groups received infusions of ACSF followed by ACSF, ACSF followed by (RS)-3,5-DHPG (50 μmol), ACSF followed by the group I mGluR antagonist MPEP, or MPEP followed by (RS)-3,5-DHPG (50 μmol), ACSF followed by the PKD1 inhibitor followed by (RS)-3,5-DHPG (50 μmol).
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Dosage form
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50 μmol (RS)-3,5-DHPG for 5 days
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Applications
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Impairments of spatial memory induced by bilateral infusions of (RS)-3,5-DHPG (50 μmol) into the CA1 area. Dose-dependent changes in spatial memory induced by (RS)-3,5-DHPG infusion. Pre-infusion of MPEP or CID755673 prevented impairments of spatial memory induced by (RS)-3,5-DHPG infusion.
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参考文献:
[1]. Gao F, Li F, et,al. Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal Müller cells. Neurosci Lett. 2015 Feb 19;588:12-7. doi: 10.1016/j.neulet.2014.12.048. Epub 2014 Dec 27. PMID: 25549543.
[2]. Wang W, Duclot F, et,al. Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats. PLoS One. 2018 Apr 3;13(4):e0195095. doi: 10.1371/journal.pone.0195095. PMID: 29614089; PMCID: PMC5882104.
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